The objective of this project is to study the macromolecular permeability of the myocardial capillaries and glomerular and peritubular capillaries in the kidney of rats and dogs under the condition of experimental diabetes mellitus. By administering in i.v. continuous infusion labelled albumin, high density plasma lipoprotein and highly homogeneous fractions of dextran molecules of varying size and measuring the concentration of these tracers in arterial plasma and in renal hilar and capsular, myocardial and thoracic duct lymph samples, the sieving property of the capillary wall and interstitium will be determined. Moreover, by studying the transient phase of the lymph concentration as a response to the initiation of the infusion and to a single i.v. injection of the tracers, information will be obtained concerning the capacity of the capillary wall and associated structures to contain macromolecules. The latter information will be derived through determination of the transfer function of the system by means of deconvolution and/or Fourier analysis. This investigation will provide quantitative data on the functional abnormality that accompanies experimental diabetic microangiopathy in the kidney and in the heart. The significance of this study is underlined by the fact that myocardial and kidney disease as a consequence of diabetic microangiopathy is among the most common and serious complications of chronic human diabetes.